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Br J Haematol. 2018 Mar;180(6):821-830. doi: 10.1111/bjh.15058. Epub 2018 Feb 13.

Ibrutinib alone or with dexamethasone for relapsed or relapsed and refractory multiple myeloma: phase 2 trial results.

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Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Department of Oncology, Johns Hopkins University, Baltimore, MD, USA.
Division of Bone Marrow Transplantation, Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Myeloma Research, Sarah Cannon Research Institute, Nashville, TN, USA.
Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.
John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA.
Hematology and Medical Oncology, Great Lakes Cancer Management Specialists, Grosse Pointe Woods, MI, USA.
Mount Sinai Medical Center, Tisch Cancer Institute, New York, NY, USA.
Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA, USA.


Novel therapies with unique new targets are needed for patients who are relapsed/refractory to current treatments for multiple myeloma. Ibrutinib is a first-in-class, once-daily, oral covalent inhibitor of Bruton tyrosine kinase, which is overexpressed in the myeloma stem cell population. This study examined various doses of ibrutinib ± low-dose dexamethasone in patients who received ≥2 prior lines of therapy, including an immunomodulatory agent. Daily ibrutinib ± weekly dexamethasone 40 mg was assessed in 4 cohorts using a Simon 2-stage design. The primary objective was clinical benefit rate (CBR; ≥minimal response); secondary objectives included safety. Patients (n = 92) received a median of 4 prior regimens. Ibrutinib + dexamethasone produced the highest CBR (28%) in Cohort 4 (840 mg + dexamethasone; n = 43), with median duration of 9·2 months (range, 3·0-14·7). Progression-free survival was 4·6 months (range, 0·4-17·3). Grade 3-4 haematological adverse events included anaemia (16%), thrombocytopenia (11%), and neutropenia (2%); grade 3-4 non-haematological adverse events included pneumonia (7%), syncope (3%) and urinary tract infection (3%). Ibrutinib + dexamethasone produced notable responses in this heavily pre-treated population. The encouraging efficacy, coupled with the favourable safety and tolerability profile of ibrutinib, supports its further evaluation as part of combination treatment.


Bruton tyrosine kinase; dexamethasone; ibrutinib; multiple myeloma

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